Disorders of Gut-brain Interaction on the US-Mexico Border: A Survey Using Rome IV Criteria.

BACKGROUND: Disorders of gut-brain interaction (DGBI) cause a substantial health burden. Herein we studied the prevalence and characteristics of DGBI and symptoms of bloating/distension in El Paso, Texas on the US-Mexico border, providing a unique opportunity to study the effects of acculturation. METHODS: Subjects from community centers completed the Rome IV questionnaire for DGBI, short acculturation scale for Hispanics questionnaire, and bloating/distention Pictograms. Data were presented as prevalence (95% CI) and compared using χ 2 . RESULTS: Of 216 participants, 197 (127 Hispanics, 90 with English acculturation) were included and 177 completed the Pictograms. Fifty-one [25.9% (20 to 32.6)] subjects fulfilled the criteria for at least one DGBI. Globus and functional dyspepsia were the most common upper DGBI, each in [3.0% (1.1 to 6.5)]. Unspecified functional bowel disorders [8.6% (5.1 to 13.5)], followed by functional abdominal bloating/distention [8.1% (4.7 to 12.9], and irritable bowel syndrome [6.1% (3.2 to 10.4] were the most common functional bowel disorder. Ninety-one (51.4%) reported bloating and/or distension with Pictograms; more frequently in those with DGBI (80.9% vs 40.8%, P < 0.001). Bloating and/or distension were reported by Pictograms in 30% of those not reporting it in the Rome IV Questionnaire. There were no differences based on acculturation or in Hispanics versus non-Hispanics. CONCLUSIONS: On the US-Mexico border, we found a lower prevalence of DGBI than in the US or Mexico. Functional abdominal bloating/distention was more prevalent on the US-Mexico border than in either country. Bloating/distension was more commonly reported with Pictograms than with verbal descriptors. There were no differences between Hispanics and non-Hispanics, suggesting shared environmental/acquired including dietary factors as the underlying mechanisms.

Efficacy of the Combination of Pinaverium Bromide 100 mg Plus Simethicone 300 mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial.

GOALS: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). BACKGROUND: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. MATERIALS AND METHODS: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, double-blind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. RESULTS: A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events. CONCLUSIONS: PB+S was superior to placebo in improving abdominal pain and bloating in patients with active IBS. The effect on the frequency of stool consistency was particularly significant in IBS-C and IBS-M.

Irritable Bowel Syndrome on the US Mexico Border: A Survey in an Indigent Population Using Rome III Criteria.

GOALS: To investigate the prevalence of irritable bowel syndrome (IBS), and its association with health perception and health care-seeking behavior in this Mexican American population. BACKGROUND: The prevalence of IBS ranges from 3% to 20.4% in the United States and 4.4% to 16% in Mexico, based on Rome III and II criteria. However, its epidemiological profile in the US Mexico border is unknown. STUDY: We conducted a survey in a randomly selected indigent population (N=521) recruited into a colon cancer screening program (ACCION). The prevalence of IBS was estimated and a multivariable logistic regression was carried out to determine the associated risk factors. Results are summarized using odds ratio and 95% confidence interval (CI). RESULTS: A total of 464 (89%) completed the survey (mean age, 56.7 y; female, 74.8%). Country of birth was Mexico in 90.5% and the United States in 8.2% and acculturation was more Spanish (94.8%) than English (5.2%). Overall, 5.6% (95% CI, 3.7-8.1) fulfilled criteria for IBS with a predominance among women (6.9%) versus men (1.7%) (P=0.03). On the basis of multivariable analysis, lower number of bowel movements/week (odds ratio, 0.89; 95% CI, 0.80-1.00), having a primary care physician: 4.09 (1.51-11.12), using herbal treatments: 2.76 (1.08-7.06) and a previous IBS diagnosis: 23.11 (3.44-155.45), were significantly associated with the presence of IBS. CONCLUSIONS: The prevalence of IBS on the US Mexico border is comparable with data obtained from studies in both countries. Consulting a primary care physician as an associated factor may reveal the high rate of health-care seeking in IBS patients, while herbal treatments may reflect a cultural influence.

Design of Treatment Trials for Functional Gastrointestinal Disorders.

This article summarizes recent progress and regulatory guidance on design of trials to assess the efficacy of new therapies for functional gastrointestinal disorders (FGIDs). The double-masked, placebo-controlled, parallel-group design remains the accepted standard for evaluating treatment efficacy. A control group is essential, and a detailed description of the randomization process and concealed allocation method must be included in the study report. The control will most often be placebo, but for therapeutic procedures and for behavioral treatment trials, respectively, a sham procedure and control intervention with similar expectation of benefit, but lacking the treatment principle, are recommended. Investigators should be aware of, and attempt to minimize, expectancy effects (placebo, nocebo, precebo). The primary analysis should be based on the proportion of patients in each treatment arm who satisfy a treatment responder definition or a prespecified clinically meaningful change in a patient-reported outcome measure. Data analysis should use the intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include secondary outcome measures to support or explain the primary outcome and an analysis of harms data. Trials should be registered in a public location before initiation and results should be published regardless of outcome.

A review of three educational projects using interactive theater to improve physician-patient communication when treating patients with irritable bowel syndrome.

BACKGROUND: Quality communication skills and increased multicultural sensitivity are universal goals, yet teaching them have remained a challenge for educators. OBJECTIVE: To document the process and participant responses to Interactive Theater when used as a method to teach physician/patient communication and cross-cultural competency. DESIGN, SETTING, AND PARTICIPANTS: Three projects are reported. They were collaborations between Theater Delta, the UNC Center for Functional GI and Motility Disorders, the Rome Foundation, the World Gastroenterology Organization, and the American Gastroenterological Association. OUTCOME MEASURES: 8 forced choice and 6 open ended were collected from each participant using a post-performance evaluation form. RESULTS: Responses to the 8 indicators relating to a positive experience participating in the Interactive Theater. The vast majority either agreed or strongly agreed with the statements on the evaluation form. Written comments explained why. CONCLUSIONS: Data indicates that Interactive Theater stimulates constructive dialogue, analysis, solutions, and intended behavior change with regard to communication skills and adapting to patients from multicultural backgrounds. Interactive Theater directly focuses on communication itself (active listening, empathy, recognizing cultural differences, etc.) and shows promise as an effective way to improve awareness and skills around these issues.

Pictograms to assess bloating and distension symptoms in the general population in Mexico: Results of The Rome Foundation Global Epidemiology Study.

BACKGROUND: There is no term for bloating in Spanish and distension is a very technical word. "Inflammation"/"swelling" are the most frequently used expressions for bloating/distension in Mexico, and pictograms are more effective than verbal descriptors (VDs) for bloating/distension in general GI and Rome III-IBS patients. However, their effectiveness in the general population and in subjects with Rome IV-DGBI is unknown. We analyzed the use of pictograms for assessing bloating/distension in the general population in Mexico. METHODS: The Rome Foundation Global Epidemiology Study (RFGES) in Mexico (n = 2001) included questions about the presence of VDs "inflammation"/"swelling" and abdominal distension, their comprehension, and pictograms (normal, bloating, distension, both). We compared the pictograms with the Rome IV question about the frequency of experiencing bloating/distension, and with the VDs. KEY RESULTS: "Inflammation"/"swelling" was reported by 51.5% and distension by 23.8% of the entire study population; while 1.2% and 25.3% did not comprehend "Inflammation"/"swelling" or distension, respectively. Subjects without (31.8%) or not comprehending "inflammation"/"swelling"/distension (68.4%) reported bloating/distension by pictograms. Bloating and/or distension by the pictograms were much more frequent in those with DGBI: 38.3% (95%CI: 31.7-44.9) vs. without: 14.5% (12.0-17.0); and in subjects with distension by VDs: 29.4% (25.4-33.3) vs. without: 17.2% (14.9-19.5). Among subjects with bowel disorders, those with IBS reported bloating/distension by pictograms the most (93.8%) and those with functional diarrhea the least (71.4%). CONCLUSIONS & INFERENCES: Pictograms are more effective than VDs for assessing the presence of bloating/distension in Spanish Mexico. Therefore, they should be used to study these symptoms in epidemiological research.

Comparison of the epidemiology of disorders of gut-brain interaction in four Latin American countries: Results of The Rome Foundation Global Epidemiology Study.

BACKGROUND: In Latin America, there are scarce data on the epidemiology of DGBI. The Rome Foundation Global Epidemiology Study (RFGES) Internet survey included 26 countries, four from Latin America: Argentina, Brazil, Colombia, and Mexico, with a 40.3% prevalence of Rome IV DGBI. We aimed at comparing the prevalence of DGBI and associated factors among these countries. METHODS: The frequency of DGBI by anatomical region, specific diagnoses, sex, age, diet, healthcare access, anxiety, depression, and HRQOL, were analyzed and compared. RESULTS: Subjects included Argentina n = 2057, Brazil = 2004, Colombia = 2007, and Mexico = 2001. The most common DGBI were bowel (35.5%), gastroduodenal (11.9%), and anorectal (10.0%). Argentina had the highest prevalence of functional diarrhea (p = 0.006) and IBS-D; Brazil, esophageal, gastroduodenal disorders, and functional dyspepsia; Mexico functional heartburn (all <0.001). Overall, DGBI were more common in women vs. men and decreased with age. Bowel disorders were more common in the 18-39 (46%) vs. 40-64-year (39%) groups. Diet was also different between those with DGBI vs. those without with subtle differences between countries. Subjects endorsing criteria for esophageal, gastroduodenal, and anorectal disorders from Mexico, more commonly consulted physicians for bowel symptoms vs. those from Argentina, Brazil, and Colombia. General practitioners were the most frequently consulted, by Mexicans (50.42%) and Colombians (40.80%), followed by gastroenterologists. Anxiety and depression were more common in DGBI individuals in Argentina and Brazil vs. Mexico and Colombia, and they had lower HRQOL. CONCLUSIONS: The prevalence of upper and lower DGBI, as well as the burden of illness, psychological impact and HRQOL, differ between these Latin American countries.

Gastrointestinal symptoms and the severity of COVID-19: Disorders of gut-brain interaction are an outcome.

BACKGROUND: Many of the studies on COVID-19 severity and its associated symptoms focus on hospitalized patients. The aim of this study was to investigate the relationship between acute GI symptoms and COVID-19 severity in a clustering-based approach and to determine the risks and epidemiological features of post-COVID-19 Disorders of Gut-Brain Interaction (DGBI) by including both hospitalized and ambulatory patients. METHODS: The study utilized a two-phase Internet-based survey on: (1) COVID-19 patients' demographics, comorbidities, symptoms, complications, and hospitalizations and (2) post-COVID-19 DGBI diagnosed according to Rome IV criteria in association with anxiety (GAD-7) and depression (PHQ-9). Statistical analyses included univariate and multivariate tests. RESULTS: Five distinct clusters of symptomatic subjects were identified based on the presence of GI symptoms, loss of smell, and chest pain, among 1114 participants who tested positive for SARS-CoV-2. GI symptoms were found to be independent risk factors for severe COVID-19; however, they did not always coincide with other severity-related factors such as age >65 years, diabetes mellitus, and Vitamin D deficiency. Of the 164 subjects with a positive test who participated in Phase-2, 108 (66%) fulfilled the criteria for at least one DGBI. The majority (n = 81; 75%) were new-onset DGBI post-COVID-19. Overall, 86% of subjects with one or more post-COVID-19 DGBI had at least one GI symptom during the acute phase of COVID-19, while 14% did not. Depression (65%), but not anxiety (48%), was significantly more common in those with post-COVID-19 DGBI. CONCLUSION: GI symptoms are associated with a severe COVID-19 among survivors. Long-haulers may develop post-COVID-19 DGBI. Psychiatric disorders are common in post-COVID-19 DGBI.

Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis.

Background: Modulating gut microbiota is a potential treatment for irritable bowel syndrome (IBS). This meta-analysis explored whether fecal microbiota transplantation (FMT) is successful in treating IBS. Methods: A systematic review was performed to find trials on FMT in IBS. Ratios and relative ratios (RR) of improvement for single-arm trials (SATs) and randomized controlled trials (RCTs) were calculated, respectively. Changes in IBS Severity Scoring System (IBS-SSS) and IBS Quality of Life (IBS-QOL) instrument compared to baseline in FMT versus placebo groups were pooled. Results: In SATs, 59.5% (95% confidence interval (CI) 49.1-69.3) of IBS patients showed significant improvement. In RCTs, there were no differences between FMT and control in improvement (RR=0.93 (95% CI 0.50-1.75)) or changes in the IBS-SSS and IBS-QOL. Conclusions: FMT was not effective in IBS. Variations in FMT methods and patient factors may contribute to the heterogeneous results of the trials.

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Colonic mast cells have been proposed to be related to the pathophysiology of irritable bowel syndrome (IBS). Whether mast cell counts are altered in the small intestine, a less-explored region in patients with IBS is not completely clear. METHODS: PubMed and EMBASE were searched for case-control studies on mast cell count/density in the small intestine of patients with IBS vs controls through February 2019. Mast cell counts were separately analyzed in the duodenum, jejunum, and ileum. Data were pooled using the standardized mean difference (SMD) method. When zero was not within the 95% confidence interval (CI), the SMD was considered significant. KEY RESULTS: Data from 344 patients with IBS and 229 healthy controls from three studies in the duodenum, six in the jejunum, and five in the ileum were pooled in this meta-analysis. The number of mast cells was significantly higher in the ileum (SMD: 1.78 [95% CI: 0.89, 2.66]) of patients with IBS. Mast cell counts were not significantly different in the duodenum (SMD: 0.81 [-0.06, 1.67]) or the jejunum (SMD: 0.58 [-0.03, 1.19]) of patients with IBS vs healthy controls. CONCLUSIONS AND INFERENCES: Mast cells are increased in the small intestine of IBS vs controls, mainly in the ileum. Future studies should address whether such findings are IBS subtype or gender-dependent. Methodological variations, single-center bias, and the limited number of studies included in this meta-analysis may affect the final results.

What Is New in Rome IV.

Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the Rome criteria; the criteria may change over time as new scientific data emerge. The Rome IV was released in May 2016. The aim is to review the main changes in Rome IV. FGIDs are now called disorders of gut-brain interaction (DGBI). Rome IV has a multicultural rather than a Western-culture focus. There are new chapters including multicultural, age-gender-women's health, intestinal microenvironment, biopsychosocial, and centrally mediated disorders. New disorders have been included although not truly FGIDs, but fit the new definition of DGBI including opioid-induced gastrointestinal hyperalgesia , opioid-induced constipation , and cannabinoid hyperemesis . Also, new FGIDs based on available evidence including reflux hypersensitivity and centrally mediated abdominal pain syndrome . Using a normative survey to determine the frequency of normal bowel symptoms in the general population changes in the time frame for diagnosis were introduced. For irritable bowel syndrome (IBS) only pain is required and discomfort was eliminated because it is non-specific, having different meanings in different languages. Pain is now related to bowel movements rather than just improving with bowel movements (ie, can get worse with bowel movement). Functional bowel disorders (functional diarrhea , functional constipation , IBS with predominant diarrhea [IBS-D], IBS with predominant constipation [IBS-C ], and IBS with mixed bowel habits ) are considered to be on a continuum rather than as independent entities. Clinical applications such as diagnostic algorithms and the Multidimensional Clinical Profile have been updated. The new Rome IV iteration is evidence-based, multicultural oriented and with clinical applications. As new evidence become available, future updates are expected.

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome.

BACKGROUND/AIMS: Abnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. METHODS: Mononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c+CD206-), M2-Advanced (CD11c-CD206+CX3CR1+); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. RESULTS: In CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of "Intermediate" (CD11c+CD206+CX3CR1+) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). CONCLUSIONS: The initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

A single session of reassurance can acutely improve the self-perception of impairment in patients with IBS.

OBJECTIVE: The aim of this study was to determine the reported frequency and self-perceived importance of factors related to health care seeking by irritable bowel syndrome (IBS) patients and the effect of reassurance on these factors. METHODS: Fifty-five IBS patients, consulting for the first time, answered a questionnaire designed to evaluate these factors (FRQ), measurements of anxiety, depression, and quality of life (QoL). A thorough explanation of the disease and reassurance were given, and the FRQ was answered again. RESULTS: The frequency of factors was: pain/discomfort, 78%; cancer fear, 11%; daily function impairment, 33%; symptoms stressfulness, 60%; and none, 2%. Pain/discomfort and symptom stressfulness were considered the most important ones. Cancer fear and symptom stressfulness correlated with anxiety (P=.003, .042), depression (P=.038, .019), and daily function impairment with depression (P=.05). Cancer fear, daily function impairment, and symptom stressfulness impacted on QoL. Reassurance acutely decreased the self-perception of daily function impairment (P=.003), independent of the patient's educational level. CONCLUSIONS: Reassurance during the first consultation for IBS decreased the self-perception of impairment in daily function.

[Successful esophageal pH monitoring with Bravo capsule in patients with gastroesophageal reflux disease]. / Medición exitosa del pH esofágico con la cápsula Bravo en pacientes con enfermedad por reflujo gastroesofágico.

INTRODUCTION: Esophageal 24-h pH monitoring (24-pH) is the most useful test to diagnose and treat patients with gastroesophageal reflux disease (GERD). The traditional system for 24-pH requires transnasal introduction of a catheter with pH sensors. This technique produces discomfort, inconvenience and interference with daily activity. Recently, the Bravo pH system has been proposed as an alternative and promising method for 24-pH. In this study, the initial experience in Mexico with this system is reported. OBJECTIVE: To evaluate safety, tolerability and performance of the pH Bravo capsule in patients with GERD. MATERIALS AND METHODS: Patients with GERD symptoms at least twice a week during the last three months, with indication for 24-pH were evaluated. pH Bravo capsule was placed 6 cm above squamocolumnar junction (SCJ). Symptoms, quality and duration of pH tracings, capsule detachment and patient global satisfaction were evaluated. RESULTS: Eleven patients (nine female, two male) mean age 42 years (range 26-62 years), two with erosive and nine with non-erosive GERD were studied. pH capsule was correctly positioned at 6 cm above SCJ in all patients. Nine patients noted a mild foreign body sensation (especially while eating) and four had mild chest pain; two patients had no discomfort. Capsule detachment occurred spontaneously in all patients on day 10. pH record for > 43 h was obtained in the 11 patients. There were no differences in pH parameters between days 1 and 2. Two patients with normal acid exposure on day 1 had abnormal pH parameters on day 2. CONCLUSIONS: Esophageal pH monitoring with Bravo capsule is a safe, reliable and tolerable method in patients with GERD. Extended pH recordings increases abnormal esophageal acid exposure detection in patients with this disease.

[Limited diagnostic testing can decrease the direct economic impact of irritable bowel syndrome]. / El escrutinio diagnóstico limitado puede disminuir el impacto económico directo del síndrome de intestino irritable (SII).

BACKGROUND: The economic impact of irritable bowel syndrome (IBS) in Mexico in terms of excessive diagnostic testing can be considerably reduced if the recommendations of the Latin American Consensus (LATAM) for IBS are followed. AIM: To estimate the economic impact of IBS in terms of excessive diagnostic testing. MATERIAL AND METHODS: Based on a previously published study, the costs of diagnostic testing for IBS were compared to the theoretical costs according to the recommendations of the consensus. These costs were compared to estimate the economic impact of excessive diagnostic testing. A cost-minimization analysis was also done. RESULTS: For the lowest socioeconomic level in academic medicine, the excessive diagnostic testing had an approximate cost of U.S. $21.38, compared to U.S. $1.72 if the LATAM Consensus recommendations would have been followed, representing a saving of 92.0%. The cost for the highest socioeconomic level in academic medicine was U.S. $1080.36 versus U.S. $103.60 (a saving of 90.4%) and for private medicine, the costs were U.S. $3121.60 versus U.S. $159.90 (a saving of 94.9%) if the recommendations would have been followed. CONCLUSIONS: Limited diagnostic testing recommended by the LATAM Consensus for IBS can significantly decrease the economic impact of this disease in Mexico

Current and future treatment of chest pain of presumed esophageal origin.

Patients with chest pain of presumed esophageal origin should be reassured and should undergo an esophageal manometry study. In patients with spastic esophageal disorders, a trial with calcium channel blockers or low-dose antidepressants used as visceral analgesics is the best approach. Inpatients with non GERD-related, nonspastic esophageal motility disorder, low-dose antidepressants seem reasonable. Anxiolytics are useful in patients with panic disorders, and psychological interventions (eg, cognitive-behavioral therapy) are also valuable, mainly in patients in whom reassurance is not sufficient to avoid the misinterpretation of their symptoms. In the future, visceral sensitivity modifying agents such as serotoninergic agonists or antagonists may become the cornerstone of therapy in patients with chest pain of presumed esophageal origin. Combinations of different approaches, such as proton pump inhibitors and psychotropic or antinociceptive agents, should also be evaluated in clinical trials.